{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T19:09:47Z","timestamp":1781291387590,"version":"3.54.1"},"reference-count":56,"publisher":"Georg Thieme Verlag KG","issue":"09","funder":[{"name":"Taishan Scholar Foundation of\n                        Shandong Province","award":["tsqn202312331"],"award-info":[{"award-number":["tsqn202312331"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of\n                        Shandong Province","doi-asserted-by":"crossref","award":["ZR2024MH347"],"award-info":[{"award-number":["ZR2024MH347"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The histone acetyltransferase KAT8 has been implicated in stem cell biology,\n                        but its specific role in human umbilical cord mesenchymal stem cells\n                        (hucMSCs) senescence and therapeutic efficacy for diabetic wounds is\n                        unclear. <\/jats:p><jats:p>This study aimed to investigate the role of KAT8 in hucMSC senescence and to\n                        determine if KAT8 knockdown could reverse senescence and enhance the\n                        efficacy of hucMSCs in promoting diabetic wound healing. <\/jats:p><jats:p>hucMSCs were extracted from the umbilical cord, and senescence was induced.\n                        KAT8 expression was assessed in senescent and non-senescent hucMSCs.\n                        Senescence markers (senescence-associated \u03b2-galactosidase [SA-\u03b2-gal]\n                        staining, P16, P21 expression), proliferation (Cell Counting Kit-8 [CCK-8],\n                        colony formation), cell migration (cell scratch), and differentiation\n                        potential (alizarin red and oil red O staining) were evaluated in vitro.\n                        Western blotting and quantitative polymerase chain reaction were performed\n                        to detect protein expression and mRNA expression levels, respectively. For\n                        in vivo studies, a type 1 diabetes mellitus mouse wound healing model was\n                        established. Mice received local injections of phosphate-buffered saline\n                        (PBS), hucMSCs transduced with a negative control vector (NC hucMSCs), or\n                        KAT8-knockdown hucMSCs. Wound closure rates were monitored, and histological\n                        analyses (Hematoxylin and eosin [H&amp;E], Masson staining). <\/jats:p><jats:p>KAT8 expression decreased during hucMSCs senescence. Knockdown of KAT8\n                        downregulated senescence-associated genes (e.g., P21 and P16) while\n                        enhancing hucMSCs proliferation, migration, and survival without altering\n                        surface stem cell marker expression. In vivo experiments further confirm\n                        that KAT8-knockdown hucMSCs significantly promoted wound healing in a type 1\n                        diabetic mouse model, exhibiting superior therapeutic efficacy.<\/jats:p><jats:p>Knockdown of KAT8 effectively reverses senescence in hucMSCs and enhances\n                        their therapeutic potential for diabetic wound healing.<\/jats:p>","DOI":"10.1055\/a-2684-5975","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T22:39:26Z","timestamp":1755297566000},"page":"441-452","source":"Crossref","is-referenced-by-count":1,"title":["KAT8 Knockdown Reverses hucMSC Senescence and Enhances Diabetic Wound\n                    Healing Efficacy"],"prefix":"10.1055","volume":"133","author":[{"given":"Ruijing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Qilu\n                    Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Qilu\n                    Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-1074","authenticated-orcid":false,"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Qilu\n                    Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"M F 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Chen","year":"2023","journal-title":"Cell Tissue Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.18632\/aging.203960","article-title":"Hallmarks of aging-based dual-purpose disease and age-associated targets\n                    predicted using PandaOmics AI-powered discovery engine","volume":"14","author":"F W Pun","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/scrt353","article-title":"Human umbilical cord mesenchymal stromal cells in regenerative medicine","volume":"4","author":"M S Detamore","year":"2013","journal-title":"Stem Cell Res Ther"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/978-1-60761-999-4_5","article-title":"Isolation, culture, and characterization of human umbilical cord stroma-derived\n                    mesenchymal stem cells","volume":"698","author":"A Can","year":"2011","journal-title":"Methods Mol 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Yao","year":"2019","journal-title":"FASEB J"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s13287-023-03345-0","article-title":"Stem cell-derived exosomes: emerging therapeutic opportunities for wound\n                    healing","volume":"14","author":"C Zhou","year":"2023","journal-title":"Stem Cell Res Ther"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"9356","DOI":"10.3390\/ijms24119356","article-title":"The potential of MSC-based cell-free therapy in wound healing\u2014a thorough\n                    literature review","volume":"24","author":"H Ma","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"951512","DOI":"10.1155\/2014\/951512","article-title":"Mesenchymal stem cells for regenerative therapy: optimization of cell\n                    preparation protocols","volume":"2014","author":"C Ikebe","year":"2014","journal-title":"BioMed Res Int"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7159465","article-title":"Therapeutic effect of human umbilical cord mesenchymal stem cells at various\n                    passages on acute liver failure in rats","volume":"2018","author":"Y Zhang","year":"2018","journal-title":"Stem Cells Int"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1007\/s00018-009-0242-9","article-title":"Histone deacetylase controls adult stem cell aging by balancing the expression\n                    of polycomb genes and jumonji domain containing 3","volume":"67","author":"J W Jung","year":"2010","journal-title":"Cell Mol Life Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1111\/j.1365-2184.2009.00633.x","article-title":"Histone deacetylase inhibitors decrease proliferation potential and multilineage\n                    differentiation capability of human mesenchymal stem cells","volume":"42","author":"S Lee","year":"2009","journal-title":"Cell Prolif"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-020-01785-6","article-title":"Impaired autophagy triggered by HDAC9 in mesenchymal stem cells accelerates bone\n                    mass loss","volume":"11","author":"L Zhang","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/s1097-2765(01)00301-x","article-title":"Highly specific antibodies determine histone acetylation site usage in yeast\n                    heterochromatin and euchromatin","volume":"8","author":"N Suka","year":"2001","journal-title":"Mol Cell"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/jbmr.2704","article-title":"Histone acetyltransferase GCN5 regulates osteogenic differentiation of\n                    mesenchymal stem cells by inhibiting NF-\u03baB","volume":"31","author":"P Zhang","year":"2016","journal-title":"J Bone Miner Res"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41419-017-0231-0","article-title":"Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of\n                    BMSCs during osteoporosis","volume":"9","author":"H Jing","year":"2018","journal-title":"Cell Death Dis"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"27253","DOI":"10.1074\/jbc.272.43.27253","article-title":"The histone acetyltransferase activity of human GCN5 and PCAF is stabilized by\n                    coenzymes","volume":"272","author":"J E Herrera","year":"1997","journal-title":"J Biol Chem"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1002\/stem.2424","article-title":"Histone H3K9 acetyltransferase PCAF is essential for osteogenic differentiation\n                    through bone morphogenetic protein signaling and may be involved in\n                    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Qiu","year":"2023","journal-title":"Cell Death Dis"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"12325","DOI":"10.1073\/pnas.1102789108","article-title":"Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and\n                    premature senescence in Zmpste24-deficient mice","volume":"108","author":"V Krishnan","year":"2011","journal-title":"Proc Natl Acad Sci"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2698","DOI":"10.1038\/onc.2015.335","article-title":"MOF maintains transcriptional programs regulating cellular stress response","volume":"35","author":"B Sheikh","year":"2016","journal-title":"Oncogene"}],"container-title":["Experimental and Clinical Endocrinology &amp; 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